Human mast cell outgrowth from CD34+ bone marrow derived cells is inhibited by IFN-gamma, but not IFN-alpha2b, and this inhibitory effect is not abrogated by IL-4. Murine mast cell lines, murine bone marrow-cultured mast cells, and peritoneal mast cells express Fas antigen. Mast cells cultured from Fas-deficient lpr mice do not express Fas antigen. Cross linking of Fas antigen with anti-Fas antibodies induces apoptosis in C57 cells, and in the presence of the transcription inhibitor actinomycin D, also in bone marrow-cultured mast cells. Mast cells attach to fibronectin and laminin following aggregation of FcgammaRII/III. Signaling through FcR that leads to adhesion requires participation of the gamma chain. Mast cells adhere to laminin after activation in part through an alpha6 containing integrin. Adhesion to laminin through alpha6 does not affect the proliferation of mast cells, but does increase mediator release after FcepsilonRI aggregation. A 95 kD protein becomes phosphorylated after adhesion to laminin. C3a and C5a are potent chemotaxins for the human mast cell line HMC-1. Chemotaxis is blocked by pertussis toxin. C3a and C5a also induce transient increases in intracellular calcium. Chemotaxis of mast cells to C3a exceeds chemotaxis to stem cell factor. This chemoattraction of mast cells to C3a and C5a may help explain the accumulation of mast cells at sites of inflammation.